Many substances such as tylosin, carbomycin, leucomycin and rosamicin are known as 16-membered macrolide antibiotics. Of these, tylosin is one of the oldest 16-membered macrolide antibiotics. Tylosin itself shows high antibacterial activity in vitro. But since its absorbability and excretability in vivo are low, much work has been done for the preparation of tylosin derivatives having excellent absorbability and excretability by chemical or biological converting methods.
From a different standpoint from prior studies, the present inventors have made investigations in order to search for novel analogous compounds of tylosin. When they cultivated a bacterial strain belonging to the genus Streptomyces having the ability of bond mycarose to the hydroxyl group at the 4'-position of the mycaminose of mycaminosyl tylonolide, acetylate the hydroxyl group at the 3-position of the tylonolide and further isovalerylate the hydroxyl group at the 4"-position of mycarose in a nutrient medium containing mycaminosyl tylonolide as a substrate, they obtained 2'-O-acetyl-4"-O-isovaleryl-23-demycinosyl-tylosin which is a compound corresponding to R.sup.1-1 =acetyl and R.sup.3-1 =isovaleryl in the following formula ##STR4## wherein R.sup.1-1 represents a hydrogen atom or an acetyl group and
R.sup.3-1 represents a hydrogen atom or an isovaleryl group. PA1 R.sup.3 represents a hydrogen atom or the group --COCH.sub.2 R.sup.5 in which R.sup.5 represents a lower alkyl group or an aryl or pyridyl group bonded through a sulfur atom; PA1 R.sup.4 represents a methyl group which may be substituted by aryl, pyridyl, pyridylthio, hydroxyl or arylthioamio, an aryl group, a nitrile group, a 5- or 6-membered heterocyclic group having 1 to 4 hetero atoms selected from nitrogen and sulfur atoms, or a tetrahydropyranyl group which may be substituted by methoxy; PA1 A represents the group --OCO--, --OSO--.sub.2 --, --O-- or --S--, or A and R.sup.4, taken together, represent a hydrogen atom, a nitrile group or a group of the formula ##STR6## in which R.sup.6 represents two lower alkyl groups, the group ##STR7## or an alkylene group having 4 to 6 carbon atoms which may have in the chain an oxygen atom or a lower alkyl-substituted nitrogen atom; and said aryl group and heterocyclic group may optionally be substituted by a methyl, methoxy or nitro group, and when R.sup.1 represents a lower alkyl group, PA1 R.sup.3 does not represent a lower alkyl group; PA1 X represents a halogen atom, PA1 R.sup.4 is as defined above; PA1 A' represents the group --OCO-- or --S--; PA1 R.sup.4 and A' taken together represent a nitrile group or a group of the formula ##STR64## in which R.sup.6 is as defined; and Y represents a hydrogen, sodium or potassium atom, to substitute the halogen atom bonded to the carbon atom at the 23-position of the compound of formula (I-b) by the group R.sup.4 --A', and as required, acylating the hydroxyl group at the 4"-position.
The present inventors named this compound "N-1 substance," and applied it for a patent (Japanese Laid-Open Patent Publication No. 43013/1980).
The present inventors also made investigations in order to mutate Streptomyces fradiae (NRRL B-2702 strain), which is a tylosin-producing strain, under various conditions. When the Streptomyces fradiae NRRL B-2702 was mutated by using N-methyl-N'-nitro-N-nitrosoguanidine as a mutation inducing agent and the resulting novel mutant, Streptomyces fradiae YO-9010, was cultivated in a nutrient medium, a compound of the above formula (I-a) in which R.sup.1-1 is a hydrogen atom and R.sup.3-1 is a hydrogen atom (23-demycinosyltylosin) with the elimination of the mysinose residue bonded to the carbon atom at the 23-position was obtained from the culture broth. The present inventors named this compound "antibiotic YO-9010", and applied it for a patent (Japanese Patent Application No. 44127/1981). The above compound and its lower alkyl ester derivatives were developed independently of the present inventors and recently disclosed (U.S. Pat. No. 4,321,361).